Inactivation of lmo0946 (sif) induces the SOS response and MGEs mobilization and silences the general stress response and virulence program in Listeria monocytogenes.

Bacteria have evolved numerous regulatory pathways to survive in changing environments. The SOS response is an inducible DNA damage repair system that plays an indispensable role in bacterial adaptation and pathogenesis. Here we report a discovery of the previously uncharacterized protein Lmo0946 as an SOS response interfering factor (Sif) in the human pathogen Listeria monocytogenes. Functional genetic studies demonstrated that sif is indispensable for normal growth of L. monocytogenes in stress-free as well as multi-stress conditions, and sif contributes to susceptibility to ß-lactam antibiotics, biofilm formation and virulence. Absence of Sif promoted the SOS response and elevated expression of mobilome genes accompanied by mobilization of the A118 prophage and ICELm-1 mobile genetic elements (MGEs). These changes were found to be associated with decreased expression of general stress response genes from the σB regulon as well as virulence genes, including the PrfA regulon. Together, this study uncovers an unexpected role of a previously uncharacterized factor, Sif, as an inhibitor of the SOS response in L. monocytogenes.

Current and Near-Future Treatment of Alzheimer's Disease.

Recent findings have improved our understanding of the multifactorial nature of AD. While in early asymptomatic stages of AD, increased amyloid-ß synthesis and tau hyperphosphorylation play a key role, while in the latter stages of the disease, numerous dysfunctions of homeostatic mechanisms in neurons, glial cells, and cerebrovascular endothelium determine the rate of progression of clinical symptoms. The main driving forces of advanced neurodegeneration include increased inflammatory reactions in neurons and glial cells, oxidative stress, deficiencies in neurotrophic growth and regenerative capacity of neurons, brain insulin resistance with disturbed metabolism in neurons, or reduction of the activity of the Wnt-ß catenin pathway, which should integrate the homeostatic mechanisms of brain tissue. In order to more effectively inhibit the progress of neurodegeneration, combination therapies consisting of drugs that rectify several above-mentioned dysfunctions should be used. It should be noted that many widely-used drugs from various pharmacological groups, "in addition" to the main therapeutic indications, have a beneficial effect on neurodegeneration and may be introduced into clinical practice in combination therapy of AD. There is hope that complex treatment will effectively inhibit the progression of AD and turn it into a slowly progressing chronic disease. Moreover, as the mechanisms of bidirectional communication between the brain and microbiota are better understood, it is expected that these pathways will be harnessed to provide novel methods to enhance health and treat AD.

Device associated -health care associated infections monitoring, prevention and cost assessment at intensive care unit of University Hospital in Poland (2015-2017).

BACKGROUND: Device-associated health care-associated infections (DA-HAIs) in intensive care unit (ICU) patients constitute a major therapeutic issue complicating the regular hospitalisation process and having influence on patients' condition, length of hospitalisation, mortality and therapy cost. METHODS: The study involved all patients treated > 48 h at ICU of the Medical University Teaching Hospital (Poland) from 1.01.2015 to 31.12.2017. The study showed the surveillance and prevention of DA-HAIs on International Nosocomial Infection Control Consortium (INICC) Surveillance Online System (ISOS) 3 online platform according to methodology of the INICC multidimensional approach (IMA). RESULTS: During study period 252 HAIs were found in 1353 (549F/804M) patients and 14,700 patient-days of hospitalisation. The crude infections rate and incidence density of DA-HAIs was 18.69% and 17.49 ± 2.56 /1000 patient-days. Incidence density of ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CLA-BSI) and catheter-associated urinary tract infection (CA-UTI) per 1000 device-days were 12.63 ± 1.49, 1.83 ± 0.65 and 6.5 ± 1.2, respectively. VAP(137) constituted 54.4% of HAIs, whereas CA-UTI(91) 36%, CLA-BSI(24) 9.6%.The most common pathogens in VAP and CA-UTI was multidrug-resistant (MDR) Acinetobacter baumannii (57 and 31%), and methicillin-resistant Staphylococcus epidermidis (MRSE) in CLA-BSI (45%). MDR Gram negative bacteria (GNB) 159 were responsible for 63.09% of HAIs. The length of hospitalisation of patients with a single DA-HAI at ICU was 21(14-33) days, while without infections it was 6.0 (3-11) days; p = 0.0001. The mortality rates in the hospital-acquired infection group and no infection group were 26.1% vs 26.9%; p = 0.838; OR 0.9633;95% CI (0.6733-1.3782). Extra cost of therapy caused by one ICU acquired HAI was US$ 11,475/Euro 10,035. Hand hygiene standards compliance rate was 64.7%, while VAP, CLA-BSI bundles compliance ranges were 96.2-76.8 and 29-100, respectively. CONCLUSIONS: DA-HAIs was diagnosed at nearly 1/5 of patients. They were more frequent than in European Centre Disease Control report (except for CLA-BSI), more frequent than the USA CDC report, yet less frequent than in limited-resource countries (except for CA-UTI). They prolonged the hospitalisation period at ICU and generated substantial additional costs of treatment with no influence on mortality. The Acinetobacter baumannii MDR infections were the most problematic therapeutic issue. DA-HAIs preventive methods compliance rate needs improvement.

The central diabetes insipidus associated with septo-optic dysplasia (de Morsier syndrome).

INTRODUCTION: Septo-optic dysplasia (SOD) is a rare congenital heterogeneous malformation with postulated genetic and environmental etiology. Septo-optic dysplasia is characterized by classic triad: optic nerve hypoplasia, midline brain malformation and hypothalamic-pituitary endocrine deficiencies. The most common hormonal deficiencies affect growth hormone and gonadotropin but it can also be lower levels of the other hormones. The rarest form of hormone deficiency is the deficiency of the antidiuretic hormone. CASE REPORT: The boy was born in 39th week of pregnancy in general good condition. Weakened suction reflex and spitting resulted in substantial difficulties with breastfeeding. After transfontanelle ultrasonography central nervous system defect was suspected. In the 5th month of life MRI confirmed septo-optic dysplasia on the basis of anterior genu of corpus callosum and septum pellucidum agenesis, both optic nerves and optic chiasm hypoplasia, pachygyria and polimicrogyria of the right frontoparietal cortex. Neurological examination revealed axial laxity, psychomotor development delay, difficulties in keeping eyes fixed as well as rotary and horizontal nystagmus. At the age of 3 years he underwent the endocrinological consultation due to polydipsia and polyuria. The tests revealed lower urine specific gravity tests results, therefore diabetes insipidus was diagnosed. The boy still receives desmopressin and there are no signs of central diabetes insipidus. Currently, the boy is under a multi-disciplinary medical care. CONCLUSIONS: The attention should be focussed on early diagnosis, mutli-specialized care and treatment SOD. Hypopituitarism ranges from isolated to multiple hormone deficits, with diabetes insipidus in a minority. Although rare, SOD is an important cause of congenital hypopituitarism and should be considered in all children with midline defects and optic nerve hyploplasia.